Bellamy M F, McDowell I F, Ramsey M W, Brownlee M, Bones C, Newcombe R G, Lewis M J
Cardiovascular Sciences Research Group and Department of Medical Computing and Statistics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Circulation. 1998 Nov 3;98(18):1848-52. doi: 10.1161/01.cir.98.18.1848.
Elevated plasma homocysteine is a risk factor for arteriosclerosis, but a cause-and-effect relationship remains to be fully established. Endothelial dysfunction, an early event in the atherogenic process, has been shown to be associated with hyperhomocysteinemia in experimental and human studies. To further establish a direct relationship between changes in plasma homocysteine and endothelial dysfunction, we investigated whether moderate hyperhomocysteinemia induced by an oral methionine load would acutely impair flow-mediated endothelium-dependent vasodilatation in healthy adults.
Twenty-four healthy volunteers completed a randomized crossover study in which an oral methionine load (0.1 g/kg) was administered on 1 of 2 study days, 7 days apart. At each visit, plasma homocysteine and brachial artery endothelium-dependent and -independent dilatation were measured at baseline and at 4 hours. To further elucidate the temporal relationship between methionine, homocysteine, and endothelial function, an oral methionine load was administered in 10 subjects on a separate visit, and the time courses of plasma methionine, homocysteine, and flow-mediated brachial artery dilatation were measured at baseline and after 1, 2, 3, 4, and 8 hours. After oral methionine, plasma homocysteine increased from 7. 9+/-2.0 micromol/L at baseline to 23.1+/-5.4 micromol/L at 4 hours (P<0.0001, n=24) and was associated with a decrease in flow-mediated brachial artery dilatation from 0.12+/-0.09 to 0.06+/-0.09 mm (P<0. 05). The time course of the impairment of flow-mediated vasodilatation mirrored the time course of the increase in homocysteine concentration.
Oral methionine loading raises plasma homocysteine and impairs flow-mediated endothelium-dependent vasodilatation. This supports the view that homocysteine may promote vascular disease by inducing endothelial dysfunction.
血浆同型半胱氨酸水平升高是动脉硬化的一个危险因素，但因果关系仍有待充分确立。内皮功能障碍是动脉粥样硬化形成过程中的早期事件，在实验和人体研究中已显示其与高同型半胱氨酸血症有关。为了进一步确立血浆同型半胱氨酸变化与内皮功能障碍之间的直接关系，我们研究了口服甲硫氨酸负荷诱导的中度高同型半胱氨酸血症是否会急性损害健康成年人血流介导的内皮依赖性血管舒张功能。
24名健康志愿者完成了一项随机交叉研究，在相隔7天的2个研究日中的1天给予口服甲硫氨酸负荷（0.1 g/kg）。每次访视时，在基线和4小时时测量血浆同型半胱氨酸以及肱动脉内皮依赖性和非依赖性舒张功能。为了进一步阐明甲硫氨酸、同型半胱氨酸和内皮功能之间的时间关系，在一次单独的访视中对10名受试者给予口服甲硫氨酸负荷，并在基线以及1、2、3、4和8小时后测量血浆甲硫氨酸、同型半胱氨酸和血流介导的肱动脉舒张功能的时间进程。口服甲硫氨酸后，血浆同型半胱氨酸从基线时的7.9±2.0 μmol/L升至4小时时的23.1±5.4 μmol/L（P<0.0001，n=24），并与血流介导的肱动脉舒张功能从0.12±0.09降至0.06±0.09 mm相关（P<0.05）。血流介导的血管舒张功能受损的时间进程与同型半胱氨酸浓度升高的时间进程一致。
口服甲硫氨酸负荷可升高血浆同型半胱氨酸水平并损害血流介导的内皮依赖性血管舒张功能。这支持了同型半胱氨酸可能通过诱导内皮功能障碍促进血管疾病的观点。
